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We examined whether the combination of <jats:italic>KIR3DS1<\/jats:italic>\/<jats:italic>3DL1<\/jats:italic> genes in concert with HLA-B27 genotypes is associated with susceptibility to ankylosing spondylitis (AS). Two HLA-B27-positive Caucasian populations were selected, one from Spain (71 patients and 105 controls) and another from the Azores (Portugal) (55 patients and 75 controls). All were typed for HLA-B and <jats:italic>KIR<\/jats:italic> (<jats:italic>3DS1<\/jats:italic> and <jats:italic>3DL1<\/jats:italic>) genes. Our results show that in addition to B27, the allele <jats:italic>3DS1<\/jats:italic> is associated with AS compared with B27 controls (<jats:italic>p<\/jats:italic> &lt; 0.0001 and <jats:italic>p<\/jats:italic> &lt; 0.003 in the Spanish population and Azoreans, respectively). We also observed that the association of KIR3DS1 to AS was found in combination with HLA-B alleles carrying Bw4-I80 in trans position in the Spanish population (30.9% in AS versus 15.2% in B27 controls, <jats:italic>p<\/jats:italic> = 0.02, odds ratio (OR) = 2.49) and in Azoreans (27.2% in AS versus 8.7% in B27 controls, <jats:italic>p<\/jats:italic> = 0.01, OR = 4.4 in Azoreans). On the other hand, 3DL1 was decreased in patients compared with B27 controls (<jats:italic>p<\/jats:italic> &lt; 0.0001 in the Spanish population and <jats:italic>p<\/jats:italic> &lt; 0.003 in Azoreans). The presence of this allele in combination with Bw4-I80 had a protective effect against the development of AS in the Spanish population (19.7% in AS, 35.2% in B27 controls; <jats:italic>p<\/jats:italic> = 0.03, OR = 0.45). The presence of <jats:italic>KIR3DS1<\/jats:italic> or <jats:italic>KIR3DL1<\/jats:italic> in combination with HLA-B*27s\/HLA-B Bw4-I80 genotypes may modulate the development of AS. The susceptibility to AS could be determined by the overall balance of activating and inhibitory composite <jats:italic>KIR<\/jats:italic>-HLA genotypes.<\/jats:p>","DOI":"10.1186\/ar1988","type":"journal-article","created":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T00:12:39Z","timestamp":1341447159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Contribution of KIR3DL1\/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations"],"prefix":"10.1186","volume":"8","author":[{"given":"Carlos","family":"Lopez-Larrea","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Blanco-Gelaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Torre-Alonso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacome Bruges","family":"Armas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Suarez-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Pruneda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Rita","family":"Couto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Segundo","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lopez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Martinez-Borra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,6,28]]},"reference":[{"key":"1865_CR1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.2174\/1566524043479284","volume":"4","author":"AM Sims","year":"2004","unstructured":"Sims AM, Wordsworth BP, Brown MA: Genetic susceptibility to ankylosing spondylitis. 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